Featured
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Review Article |
Insights into the success and failure of systemic therapy for hepatocellular carcinoma
The design of clinical trials for hepatocellular carcinoma is complicated by a number of obstacles. In this Review, the authors discuss the advances in systemic therapy for hepatocellular carcinoma and critically discuss trial designs in the context of past successes and failures.
- Jordi Bruix
- , Leonardo G. da Fonseca
- & María Reig
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Research Highlight |
Mapping the cells in the liver — unchartered subtypes and heterogeneity
- Katrina Ray
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News & Views |
The jigsaw of dual hepatocellular–intrahepatic cholangiocarcinoma tumours
A new study involving integrative genomic and transcriptomic analysis of dual hepatocellular–intrahepatic cholangiocarcinoma tumours has identified distinct subtypes that display different clinical and molecular features, and that could be used to guide therapeutic decisions.
- Patricia Munoz-Garrido
- & Pedro M. Rodrigues
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Review Article |
The role of telomeres and telomerase in cirrhosis and liver cancer
Telomerase is a key enzyme for cell survival that prevents telomere shortening. In this Review, the roles of telomeres and telomerase in cirrhosis and liver carcinogenesis are discussed, in addition to their potential in clinical practice as biomarkers and therapeutic targets.
- Jean-Charles Nault
- , Massih Ningarhari
- & Jessica Zucman-Rossi
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News & Views |
The effects of platelet accumulation in fatty liver disease
A new study provides evidence that platelets exert potent inflammatory effects and play a central part in the progression from simple steatosis to nonalcoholic steatohepatitis. The results from this and other studies raise important questions regarding the role of platelets in the development of hepatocellular carcinoma in individuals with fatty liver disease.
- Laurence P. Diggs
- & Tim F. Greten
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Review Article |
From NASH to HCC: current concepts and future challenges
The hepatic consequence of metabolic syndrome and obesity, nonalcoholic fatty liver disease (NAFLD), underlies many cases of hepatocellular carcinoma (HCC). In this Review, the authors discuss NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity.
- Quentin M. Anstee
- , Helen L. Reeves
- & Mathias Heikenwalder
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News & Views |
Precision dietary supplementation based on personal gut microbiota
Over the past decade, many studies have revealed the importance of the gut microbiome in disease development and treatment, including in cancer. Because both host genetics and the gut microbiome can influence host phenotype and treatment outcome, there is an urgent need to develop precision medicine and personalize dietary supplementation based on an individual’s microbiome.
- Yu-Jui Yvonne Wan
- & Prasant Kumar Jena
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Review Article |
Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators
The liver is a key metabolic organ, and alterations to hepatic metabolism are important for the development of disease. In this Review, the authors explore the central roles of peroxisome proliferator-activated receptor-γ coactivators (PGC1s) in physiological and pathophysiological settings, with a focus on nonalcoholic fatty liver disease and liver cancer.
- Elena Piccinin
- , Gaetano Villani
- & Antonio Moschetta
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Review Article |
Wnt–β-catenin signalling in liver development, health and disease
The Wnt–β-catenin pathway is a highly conserved pathway that regulates embryogenesis and key regenerative processes in adult organs. Here, the authors discuss the role of Wnt–β-catenin signalling in liver development and disease, including in liver cancer, NAFLD and liver fibrosis.
- Maria J. Perugorria
- , Paula Olaizola
- & Jesus M. Banales
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News & Views |
Gut microbiota as gatekeeper of anti-tumour responses in the liver
A new report in Science by Ma and colleagues uncovers the interplay of microbiota-controlled bile acid metabolism and immune responses in the context of primary and metastatic liver tumours in mice. Their findings shed light on the gut–liver axis in hepatic malignancies.
- Timon E. Adolph
- & Herbert Tilg
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Review Article |
Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research
Multiple methods exist to induce liver disease and hepatocellular carcinoma formation in mice. This Review provides an overview of different mouse models of hepatocellular carcinoma, discussing approaches to help choose an appropriate model and highlighting specific concepts for immunotherapy research.
- Zachary J. Brown
- , Bernd Heinrich
- & Tim F. Greten
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News & Views |
HCV therapy and risk of liver cancer recurrence: who to treat?
Recurrence of hepatocellular carcinoma after resection or ablation with curative intent is common and not prevented by direct-acting antiviral agent (DAA) therapy for hepatitis C. Owing to multiple methodological inconsistencies, available studies fail to answer whether DAA therapy anticipated risk of severe tumour recurrence: a prospective randomized study might serve the purpose.
- Massimo Colombo
- & Vincenzo Boccaccio
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Review Article |
Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications
A growing body of evidence implicates non-coding RNAs (ncRNAs) in liver carcinogenesis. In this Review, the authors summarize the pathological roles of ncRNAs in hepatocellular carcinoma and explore the potential applications of ncRNAs as diagnostic tools and therapeutic targets.
- Chun-Ming Wong
- , Felice Ho-Ching Tsang
- & Irene Oi-Lin Ng
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Year in Review |
Novel insights into mechanisms of disease progression
In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies.
- Reenam S. Khan
- & Philip N. Newsome
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Year in Review |
Two large steps forward, one small step back
In 2017, the FDA approved regorafenib and nivolumab for the treatment of patients with hepatocellular carcinoma following prior sorafenib treatment, opening the door for an effective systemic second-line therapy in advanced disease. By contrast, the addition of sorafenib to transarterial chemoembolization with drug-eluting beads did not improve progression-free survival in the intermediate disease stage.
- Marcus-Alexander Wörns
- & Peter R. Galle
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Research Highlight |
A complex interplay between inflammation and immunity in liver cancer
- Katrina Ray
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News & Views |
Sensitizing hepatocellular carcinoma to oncolytic virus therapy
Oncolytic viruses have made headlines owing to increasing numbers of reports of clinical success. Compelling data now indicate that small anticancer molecules can serve as potent sensitizers of tumour cells in hepatocellular carcinoma to enhance the oncolytic potential of systemically applied viruses.
- Jennifer Altomonte
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Review Article |
Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Bile acids link the gut microbiota to both hepatic and intestinal metabolism, and this tripartite relationship has been implicated in gastrointestinal disease. In this Review, the authors outline the mechanistic links between bile acid–microbiota crosstalk and gastrointestinal inflammation and carcinogenesis, with a specific emphasis on the major bile-acid-sensing receptors.
- Wei Jia
- , Guoxiang Xie
- & Weiping Jia
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News & Views |
Translating '–omics' results into precision medicine for hepatocellular carcinoma
A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC.
- Daniela Sia
- & Josep M. Llovet
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Review Article |
The gut microbiome and liver cancer: mechanisms and clinical translation
Increasing evidence suggests that the gut microbiota are important modulators of chronic liver disease progression and the development of hepatocellular carcinoma. In this Review, Yu and Schwabe discuss the mechanisms by which the gut microbiota promote hepatocarcinogenesis, and explore therapeutic interventions with clinical potential.
- Le-Xing Yu
- & Robert F. Schwabe
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News & Views |
Regorafenib as second-line therapy in hepatocellular carcinoma
Drug development in hepatocellular carcinoma had essentially stalled since 2008 when sorafenib was established as the modest standard of care. Now, a positive result in a phase III study evaluating regorafenib challenges us to weigh its clinical significance as well as its real-world benefits and potential harms.
- Austin G. Duffy
- & Tim F. Greten
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Review Article |
Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches
Liver transplantation is the best option for patients with early-stage hepatocellular carcinoma. Here, the authors summarize the outcomes of liver transplantation, novel surgical techniques to increase the pool of donor livers for transplantation and the limitations of current priority policies.
- Gonzalo Sapisochin
- & Jordi Bruix
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Review Article |
Global epidemiology and burden of HCV infection and HCV-related disease
Chronic HCV infection is a global health problem. In this Review, the authors describe the global burden of hepatitis C and HCV-related disease, including hepatocellular carcinoma, cirrhosis and extrahepatic manifestations. How the new direct-acting antiviral agents might influence disease burden is also discussed.
- Aaron P. Thrift
- , Hashem B. El-Serag
- & Fasiha Kanwal
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Research Highlight |
Therapy for colorectal cancer liver metastases: understanding resistance
- Katrina Ray
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News & Views |
Effect of HCV clearance with direct-acting antiviral agents on HCC
Unexpected data from new studies show that direct-acting antiviral agents might promote tumour occurrence in patients with cirrhosis, or recurrence in patients with presumed cure of hepatocellular carcinoma. In view of the potential clinical implications, this controversy calls for a thorough and expeditious consideration of the hypothetical oncogenic activity of novel HCV drugs.
- Josep M. Llovet
- & Augusto Villanueva
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Review Article |
The Hippo pathway in intestinal regeneration and disease
The Hippo signalling cascade is crucial for the maintenance of tissue homeostasis and regeneration after damage. This Review describes the core components of the Hippo pathway and their role in intestinal homeostasis, regeneration and disease, and the integration of Hippo signalling with other key signalling pathways. The function of the Hippo pathway in liver physiology and disease is briefly discussed.
- Audrey W. Hong
- , Zhipeng Meng
- & Kun-Liang Guan
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News & Views |
HCV compartmentalization in HCC: driver, passenger or both?
Hepatocellular carcinoma is associated with HCV infection but the underlying interplay between virus and tumour remains to be elucidated. Now, Harouaka et al. report that in patients with HCV-related cirrhosis, HCV replication is restricted within liver tissue originating from hepatocellular carcinoma, with an associated increase in the diversity and complexity of the HCV quasispecies.
- Jacinta A. Holmes
- & Raymond T. Chung
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Review Article |
Circadian rhythms of liver physiology and disease: experimental and clinical evidence
The circadian clock plays a central part in the regulation of liver function. In this Review, Tahara and Shibata discuss the mechanisms by which the circadian clock controls hepatic metabolism and the processing of xenobiotics, and how clock dysfunction can influence liver disease.
- Yu Tahara
- & Shigenobu Shibata
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Review Article |
Immunological landscape and immunotherapy of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is an antigenic lesion infiltrated by T cells, but factors within the tumour and its microenvironment dampen the immune response and prevent effective antitumour immunity. The stepwise elucidation of the various immunosuppressive mechanisms at play in HCC has exposed new therapeutic options. This Review gives a comprehensive overview of the different immunotherapeutic modalities applicable in HCC, including vaccines, adoptive T-cell therapy, cytokines, gene therapy and immune checkpoint inhibitors.
- Jesús Prieto
- , Ignacio Melero
- & Bruno Sangro
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Correspondence |
Multiple carcinogenesis contributes to the heterogeneity of HCC
- Qiang Gao
- , Xiao-Ying Wang
- & Jia Fan